Ask about this productRelated genes to: TMEM184A Blocking Peptide
- Gene:
- TMEM184A NIH gene
- Name:
- transmembrane protein 184A
- Previous symbol:
- -
- Synonyms:
- MGC9712, SDMG1
- Chromosome:
- 7p22.3
- Locus Type:
- gene with protein product
- Date approved:
- 2007-07-11
- Date modifiied:
- 2016-07-21
Related products to: TMEM184A Blocking Peptide
Related articles to: TMEM184A Blocking Peptide
- The dominance of immunotherapy-insensitive MSS colorectal cancers (CRCs), which represent most cases, contrasts sharply with the treatable MSI-H minority, making this disparity a key obstacle to progress. It is urgent to identify genes driving immune evasion in MSS CRCs. Here, using a genome-wide CRISPR screen in a syngeneic tumor model under immune pressure, we identify TMEM184A as a previously unknown tumor-intrinsic regulator of immune evasion. Its genetic deletion in murine models enhanced CD8 T cell infiltration and increased surface MHC-I expression on cancer cells, as shown by flow cytometry, immunohistochemistry, immunofluorescence and RNA-seq. Mechanistically, TMEM184A functions as a novel macroautophagy/autophagy receptor by binding GABARAPL2, directly promoting the autophagic degradation of IFNG-induced MHC-I. In murine models, genetic deletion of led to a significant increase in both CD8 T cell infiltration and surface MHC-I expression on cancer cells. Functional studies in vivo and in vitro confirmed that this impaired antigen presentation causally facilitates immune evasion. Our findings establish MHC-I autophagic degradation as a critical pathway regulating immune evasion and position TMEM184A as a pivotal molecular hub in this process. Notably, treatment with the autophagy inhibitor chloroquine significantly increased surface MHC-I levels and enhanced the efficacy of anti-PDCD1/PD-1 therapy specifically in TMEM184A-high tumors. This work suggests that targeting TMEM184A or its associated autophagic pathway could restore antigen presentation in MHC-I-deficient tumors, offering a potential combinatorial strategy to overcome adaptive immune resistance in multiple malignancies.: AKP organoids:andknockout, KRASmutation organoids; CRC: colorectal cancer; CQ: chloroquine; GABARAPL2/Atg8: GABA type A receptor associated protein like 2; IF: immunofluorescence; IFNG: interferon gamma; IHC: immunohistochemistry; MHC-I: major histocompatibility complex I; qRT-PCR: quantitative reverse transcription PCR; MSI-H: microsatellite instability-high; MSS: microsatellite-stable; TMEM184A: transmembrane proteins 184a. - Source: PubMed
Publication date: 2026/06/30
Li WenyiLi KejunShi ZhiminChen YuehongCheng MingzhenZhao BohouWang ShunyiDiao ShizheYe ShengzhiWang XianzheLi JinZhang ZijingQiao YuanyuanXiong WenjunWang WeiMa Wenhui - The cellular origin and molecular mechanisms underlying therapeutic resistance in colorectal cancer remain largely unclear.This study integrates single-cell transcriptomics, spatial transcriptomics, molecular docking, and multi-cohort public databases to systematically elucidate the epithelial cell-driven drug resistance mechanism, and combines clinical pathological paraffin samples to evaluate the clinical significance and prognosis of the key protein TMEM184A. Integrated single-cell datasets underwent quality control and PCA/UMAP clustering, followed by annotation verified through spatial transcriptomic mapping. CellChat, CopyKat, inferCNV, Monocle3 and AUCell analyses were applied to assess cell–cell communication, CNV heterogeneity and pseudotime differentiation. Integrate the TCGA, GEO data, as well as the drug sensitivity data from GSCA and CTR-DB 2.0, and combine with the AutoDock molecular docking results to explore the correlation between genes and prognosis, as well as immune infiltration, and their pharmacological effects. Use the tissue microarray technique to detect the protein expression of TMEM184A in cancer tissues and adjacent tissues, and analyze its association with clinical pathological features and patient prognosis. The study identified a subset of epithelial cells associated with drug resistance, characterized by the enrichment of interferon, TNF-α/NF-κB, TGF-β, hypoxia, and p53 signaling pathways.By combining machine learning and clinical prognosis analysis, the key drug-resistant driving gene TMEM184A was finally determined. The genes related to TMEM184A were significantly enriched in the lipid metabolism pathway. Moreover, TMEM184A were highly expressed in microsatellite stable colorectal cancer, positively correlated with regulatory T cell (Treg) infiltration, and associated with the “low immune - low stroma” microenvironment. The analysis of immunohistochemical staining on tissue microarrays showed that the high expression of TMEM184A protein was related to lymph node metastasis, and was more prevalent in the rectal region. Additionally, the high expression of TMEM184A was associated with poor prognosis in patients. Drug sensitivity and molecular docking analysis indicated that TMEM184A had strong binding affinity with lapatinib and various EGFR tyrosine kinase inhibitors. TMEM184A promotes the occurrence of drug resistance in colorectal cancer by regulating lipid metabolism. The high expression of this protein in the rectum is more common and is associated with lymph node metastasis and poor prognosis in patients with colorectal cancer. This study provides a theoretical basis for TMEM184A to be used as a prognostic marker and a therapeutic target for drug resistance in colorectal cancer. - Source: PubMed
Publication date: 2026/04/03
Bai XueliangBai ZhongyuanBu PengLiu RuijiangZhao GuohaiCui WeiCui YongpingXi Yanfeng - BACKGROUND: Although previous studies have linked colorectal cancer (CRC) with lipid metabolism and inflammatory signaling, the specific roles of phosphatidylcholine metabolites and their interactions with inflammatory cytokines in the tumor microenvironment remain poorly understood. METHODS: This study utilizes an integrated multi-omics analysis approach. We performed a two-sample Mendelian randomization analysis using data from 1400 metabolites and 91 inflammatory cytokines to investigate their associations with CRC, followed by experimental validation of the findings. Single-cell transcriptomics revealed metabolic state differences, while machine learning constructed a predictive model. SHAP analysis interpreted the model, with spatial transcriptomics validating key findings. RESULTS: The phosphatidylcholine metabolite DPPC was identified as causally associated with CRC risk. Our results demonstrated DPPC promotes tumor progression by inhibiting TNFSF14 secretion. Our DPPC-based model effectively predicted CRC progression, with SHAP analysis identifying ARL8A, MTUS1, and TMEM184A as key contributors. These findings were validated spatially and translated into a clinical nomogram for prognosis and immunotherapy guidance. In summary, this study highlights the significance of DPPC-mediated regulation within the tumor microenvironment in predicting CRC progression and guiding potential therapeutic strategies. - Source: PubMed
Publication date: 2026/01/02
Li XingDong HaifengJin ZihanYu HongZhou HaoChen JingyaoWang ChenChen SongyaoZhang ChanghuaChen Hengxing - VE-cadherin (VE-cad) membrane stability and localization regulates adhesion formation and actin cytoskeleton dynamics in angiogenesis and vascular remodeling and requires the heparan sulfate proteoglycan (HSPG), Syndecan-4 (Sdc4). This study characterizes the interactions of the heparin receptor, Transmembrane protein-184A (TMEM184A), and Sdc4 in bovine aortic endothelial cells (BAOECs) and the regenerating Zebrafish (ZF) caudal fin and measures the effect of siRNA TMEM184A KD (siTMEM) and TMEM184A overexpression (TMEM OE) on VE-cad levels and localization in confluent and sub-confluent cultured BAOECs. Additionally, we examined the effect of siTMEM on key Rab GTPase trafficking regulators and migrating BAOECs in scratch wound healing assays. We demonstrated that TMEM184A and Sdc4 colocalize in BAOECs and that Sdc4 OE increases colocalization in an HS chain dependent manner, while both Tmem184a and Sdc4 cooperate synergistically in ZF fin angiogenic and tissue repair. We also showed that siTMEM decreases VE-cad membrane and cytoplasmic levels, while increasing scratch wound migration rates. However, TMEM OE cells show increased vesicle formation and VE-cad trafficking and membrane recovery. These findings characterize TMEM184A-Sdc4 cooperation in angiogenesis and indicate a dual function of TMEM184A in signaling and trafficking in vascular cells that promotes VE-cad recovery and membrane localization. - Source: PubMed
Publication date: 2025/06/03
Altenburg Leanna MWang Stephanie HCiabattoni Grace OKennedy AmeliaO'Toole Rachel LFarwell Sara L NIovine M KathrynLowe-Krentz Linda J - Immunotherapy has opened up a new era of individualized treatment for non-small cell lung cancer (NSCLC) with negative driver gene mutations. Anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies have been the main options for immunotherapy over the past decade. Screening for predictive markers of anti-PD-1/PD-L1-responsive patients remains a focus in the field of immunotherapy, especially on the protein level in which relevant proteomic biomarkers are still lacking. - Source: PubMed
Publication date: 2024/01/29
Zhang XiaoshenGao GuanghuiZhang QianZhao SongchenLi XuefeiCao WeiLuo HengZhou Caicun